Central Venous Access Devices for the Delivery of Systemic Anticancer Therapy: An Economic Evaluation.

OBJECTIVES: Patients undergoing long-term anticancer therapy typically require one of 3 venous access devices: Hickman-type device (HICK), peripherally inserted central catheter (PICC), or implantable chest wall port (PORT). Recent evidence has shown PORT is safer and improves patient satisfaction. However, PORT did not show improvement in quality-adjusted life-years and was more expensive. Decisions regarding cost-effectiveness in the United Kingdom are typically informed by a cost-per-quality-adjusted life-year metric. However, this approach is limited in its ability to capture the full range of relevant outcomes, especially in the context of medical devices. This study assessed the potential cost-effectiveness of HICK, PICC, and PORT in routine clinical practice. METHODS: This is a cost-consequence analysis to determine the trade-offs between the following outcomes: complication, infection, noninfection, chemotherapy interruption, unplanned device removals, health utilities, device insertion cost, follow-up cost, and total cost, using data from the Cancer and Venous Access clinical trial. We conducted value of implementation analysis of a PORT service. RESULTS: PORT was superior in terms of overall complication rate compared with both HICK (incidence rate ratio 0.422; 95% CI 0.286-0.622) and PICC (incidence rate ratio 0.295; 95% CI 0.189-0.458) and less likely to lead to an unplanned device removal. There was no difference in chemotherapy interruption or health utilities. Total cost with device in situ was lower on PORT than HICK (-£98.86; 95% CI -189.20 to -8.53) and comparable with PICC -£48.57 (95% CI -164.99 to 67.86). Value of implementation analysis found that PORT was likely to be considered cost-effective within the National Health Service. CONCLUSION: Decision makers should consider including PORT within the suite of venous access devices available within in the National Health Service.

Pharmacokinetics and Safety of a Novel Oral Liquid Formulation of 13-cis Retinoic Acid in Children with Neuroblastoma: A Randomized Crossover Clinical Trial.

(1) Background: 13-cis-retinoic acid (13-CRA) is a key component of neuroblastoma treatment protocols. This randomized crossover study compares the pharmacokinetics (PK), safety and palatability of a novel oral liquid formulation to the current method of extracting 13-CRA from capsules. (2) Methods: Pharmacokinetics was evaluated in two consecutive treatment cycles. Patients were randomized to receive either liquid or capsule formulation on cycle 1 and then crossed over to the alternative formulation on cycle 2. The daily dose was 200 mg/m2, reduced to 160 mg/m2 in patients with weight ≤ 12 kg. (3) Results: A total of 20 children, median (range) age 4.3 (1-11.6) y were recruited. Pharmacokinetic data were pooled and a population model describing the disposition of 13-CRA and 4-oxo-13-CRA was developed. Bioavailability of the liquid formulation was estimated to be 65% higher (95% CI; 51-79%) than the extracted capsule. CmaxSS and AUC(0-12)SS estimates were also significantly higher; mean (95% CI) differences were 489 (144-835) ng/mL and 3933 (2020-5846) ng/mL·h, respectively (p < 0.01). There were no significant differences in reported adverse effects. Parents found dosing considerably easier with liquid formulation. (4) Conclusions: The pharmacokinetics, safety and palatability of a new liquid formulation of 13-CRA compares favorably to 13-CRA extracted from capsules. Clinical Trial Registration: clinicaltrial.gov NCT03291080.

Cardiac structure and function after revascularization versus medical therapy for renal artery stenosis: the ASTRAL heart echocardiographic sub-study.

BACKGROUND: The ASTRAL trial showed no difference in clinical outcomes between medical therapy and revascularization for atherosclerotic renal vascular disease (ARVD). Here we report a sub-study using echocardiography to assess differences in cardiac structure and function at 12 months. METHODS: ASTRAL patients from 7 participating centres underwent echocardiography at baseline and 12 months after randomisation. Changes in left ventricular ejection fraction (LVEF), left ventricular mass (LVM), left atrial diameter (LAD), aortic root diameter (AoRD), E:A, and E deceleration time (EDT) were compared between study arms. Analyses were performed using t-tests and multivariate linear regression. RESULTS: Ninety two patients were included (50 medical versus 42 revascularization). There was no difference between arms in any baseline echocardiographic parameter. Comparisons of longitudinal changes in echocardiographic measurements were: δLVEF medical 0.8 ± 8.7% versus revascularization - 2.8 ± 6.8% (p = 0.05), δLVM - 2.9 ± 33 versus - 1.7 ± 39 g (p = 0.9), δLAD 0.1 ± 0.4 versus 0.01 ± 0.5 cm (p = 0.3), δAoRD 0.002 ± 0.3 versus 0.06 ± 0.3 cm (p = 0.4), δE:A - 0.0005 ± 0.6 versus 0.03 ± 0.7 (p = 0.8), δEDT - 1.1 ± 55.5 versus - 9.0 ± 70.2 ms (p = 0.6). In multivariate models, there were no differences between treatment groups for any parameter at 12 months. Likewise, change in blood pressure did not differ between arms (mean δsystolic blood pressure medical 0 mmHg [range - 56 to + 54], revascularization - 3 mmHg [- 61 to + 59], p = 0.60). CONCLUSIONS: This sub-study did not show any significant differences in cardiac structure and function accompanying renal revascularization in ASTRAL. Limitations include the small sample size, the relative insensitivity of echocardiography, and the fact that a large proportion of ASTRAL patient population had only modest renal artery stenosis as described in the main study.

Effect of renal artery revascularization upon cardiac structure and function in atherosclerotic renal artery stenosis: cardiac magnetic resonance sub-study of the ASTRAL trial.

BACKGROUND: Cardiac abnormalities are frequent in patients with atherosclerotic renovascular disease (ARVD). The Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial studied the effect of percutaneous renal revascularization combined with medical therapy compared with medical therapy alone in 806 patients with ARVD. METHODS: This was a pre-specified sub-study of ASTRAL (clinical trials registration, current controlled trials number: ISRCTN59586944), designed to consider the effect of percutaneous renal artery angioplasty and stenting on change in cardiac structure and function, measured using cardiac magnetic resonance (CMR) imaging. Fifty-one patients were recruited from six selected ASTRAL centres. Forty-four completed the study (medical therapy n = 21; revascularization n = 23). Full analysis of CMR was possible in 40 patients (18 medical therapy and 22 revascularization). CMR measurements of left and right ventricular end systolic (LV and RVESV) and diastolic volume (LV and RVEDV), ejection fraction (LVEF) and mass (LVM) were made shortly after recruitment and before revascularization in the interventional group, and again after 12 months. Reporting was performed by CMR analysts blinded to randomization arm. RESULTS: Groups were well matched for mean age (70 versus 72 years), blood pressure (148/71 versus 143/74 mmHg), degree of renal artery stenosis (75 versus 75%) and comorbid conditions. In both randomized groups, improvements in cardiac structural parameters were seen at 12 months, but there were no significant differences between treatment groups. Median left ventricular changes between baseline and 12 months (medical versus revascularization) were LVEDV -1.9 versus -5.8 mL, P = 0.4; LVESV -2.1 versus 0.3 mL, P = 0.7; LVM -5.4 versus -6.3 g, P = 0.8; and LVEF -1.5 versus -0.8%, P = 0.7. Multivariate regression also found that randomized treatment assignment was not associated with degree of change in any of the CMR measurements. CONCLUSIONS: In this sub-study of the ASTRAL trial, renal revascularization did not offer additional benefit to cardiac structure or function in unselected patients with ARVD.

Innovation in training for totally implanted port insertion.

This article discusses the use of fresh frozen cadavers as an innovative way to teach the procedure of totally implanted port insertion. In an attempt to increase the number of competent medical and nursing practitioners able to insert these devices, workshops have been devised and delivered at a university clinical anatomy skills centre. This method of teaching has had positive feedback from practitioners.

Innovation in training for totally implanted port insertion.

This article discusses the use of fresh frozen cadavers as an innovative way to teach the procedure of totally implanted port insertion. In an attempt to increase the number of competent medical and nursing practitioners able to insert these devices, workshops have been devised and delivered at a university clinical anatomy skills centre. This method of teaching has had positive feedback from practitioners.

Hickman catheter and implantable port devices for the delivery of chemotherapy: a phase II randomised controlled trial and economic evaluation.

BACKGROUND: In the United Kingdom, totally implantable venous access systems (TIVAS) are not routinely used. Compared with Hickman catheters, these devices are more expensive and complex to insert. However, it is unclear whether the higher costs may be offset by perceived greater health benefits. This pilot trial aimed to generate relevant data to inform the design of a larger definitive randomised controlled trial. METHODS: This was a phase II prospective, randomised, open trial from two UK oncology centres. The primary end point was overall complication rate. Secondary end points included individual complication rates, time to first complication and quality of life. Analysis was by intention to treat. An economic evaluation was also carried out. RESULTS: A total of 100 patients were randomised in a 3 : 1 ratio to receive a Hickman or a TIVAS. Overall, 54% of patients in the Hickman arm suffered one or more complications compared with 38% in the TIVAS arm (one-sided P=0.068). In the Hickman arm, 28% of the devices were removed prematurely due to a complication compared with 4% in the TIVAS arm. Quality of life based on the device-specific questionnaire was greater in the TIVAS arm for 13 of the 16 questions. The economic evaluation showed that Hickman arm was associated with greater mean cost per patient £1803 (95% CI 462, 3215), but similar quality-adjusted life years -0.01 (95% CI -0.15, 0.15) than the TIVAS arm. However, there is much uncertainty associated with the results. CONCLUSIONS: Compared with Hickman catheters, TIVAS may be the cost-effective option. A larger multicentre trial is needed to confirm these preliminary findings.

A randomised trial of treating fibroids with either embolisation or myomectomy to measure the effect on quality of life among women wishing to avoid hysterectomy (the FEMME study): study protocol for a randomised controlled trial.

BACKGROUND: Uterine fibroids are the most common tumour in women of reproductive age. By the time they are 50-years-old around 80% of women will have developed one. Of these, around half will experience symptoms which will impact negatively on their quality of life. Hysterectomy is the traditional treatment for women with symptomatic fibroids. For women who do not wish to undergo a hysterectomy, two invasive treatments are commonly available: myomectomy or uterine artery embolization (UAE). DESIGN: FEMME is a pragmatic, randomised, open, multi-centre trial examining the quality of life menstruating women with symptomatic fibroids experience after treatment with UAE or myomectomy. METHODS: After providing informed consent, 216 women with symptomatic fibroids from 43 NHS Hospital Trusts and Health Boards across the United Kingdom will undergo randomisation by a centralised computer system to treatment by either UAE or myomectomy. A minimisation algorithm will be used in order to balance the groups with respect to the following three parameters: the longest dimension of the largest fibroid, the number of fibroids present, and whether the woman currently desires pregnancy.Using validated questionnaires the women's quality of life will be compared between groups at six months, one year, two years and four years post-procedure, taking into account pre-procedure scores. An economic evaluation will be conducted alongside the trial to determine the cost-effectiveness of UAE compared with myomectomy.Validated diaries will also be used to compare menstrual blood loss at the same time-points. The plasma concentration of Anti-Müllerian hormone (AMH), which will act as a proxy measurement of ovarian reserve, will be recorded before the woman has her procedure and then again at six weeks, six months, and twelve months afterwards. Re-intervention rates will be recorded. DISCUSSION: The FEMME trial's primary outcome is the quality of life women with symptomatic uterine fibroids experience two years after they have been treated with either UAE or myomectomy, as measured by the disease-specific Uterine Fibroid Symptom Quality-of-Life (UFS-QoL) questionnaire. TRIAL REGISTRATION: Current Controlled Trials registration number: ISRCTN70772394, registered on 2 March 2013.

Centrally inserted external catheters and totally implantable ports for the delivery of chemotherapy: a systematic review and meta-analysis of device-related complications.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the risks of complications (infectious and non-infectious) including the need for device removal associated with centrally inserted external catheters compared with totally implantable ports in patients undergoing chemotherapy. METHODS: Relevant major electronic databases were searched from inception to December 2012. All randomized controlled trials (RCT) and observational studies that compared centrally inserted external catheters with totally implantable ports in patients undergoing chemotherapy were included in the systematic review. Meta-analysis was carried out to estimate the odds ratios of device-associated complications, including infection, non-infectious complications and device removal associated with external catheters relative to implantable ports. RESULTS: Overall, five RCTs and 25 observational studies were included in the study. The studies were heterogeneous, and included adults and children, with different types of cancer, undergoing chemotherapy. Based on the pooled estimates from included studies, external catheters were associated with approximately a three to four-fold increase in the risks of infections, non-infectious complications and device removal compared implantable ports. CONCLUSION: The findings of this study showed that totally implantable ports are superior to external catheters in terms of catheter-associated complications. However, a formal health technology assessment on the clinical and cost-effectiveness of the use of implantable ports compared with external catheters is needed to inform policy makers of the relative value of investing in totally implantable devices compared with external catheters.

Randomized comparison of uterine artery embolization (UAE) with surgical treatment in patients with symptomatic uterine fibroids (REST trial): subanalysis of 5-year MRI findings.

PURPOSE: To report 5-year contrast-enhanced magnetic resonance imaging findings of the REST trial recruits who underwent either uterine artery embolization (UAE) or myomectomy. METHODS: A total of 157 patients were randomized to UAE or surgery (hysterectomy or myomectomy). Ninety-nine patients who had UAE and eight patients who had myomectomy were analyzed. MRI scans at baseline, 6 months, and 5 years were independently interpreted by two radiologists. Dominant fibroid diameter, uterine volume, total fibroid infarction (complete 100 %, almost complete 90-99 %, partial <90 %), and new fibroid formation were the main parameters assessed and related to the need for reintervention. RESULTS: In the UAE group, mean ± standard deviation uterine volume was 670 ± 503, 422 ± 353, and 292 ± 287 mL at baseline, 6 months, and 5 years, respectively. Mean dominant fibroid diameter was 7.6 ± 3.0, 5.8 ± 2.9, and 5 ± 2.9 cm at baseline, 6 months, and 5 years. Fibroid infarction at 6 months was complete in 35 % of women, almost complete in 29 %, and partial in 36 %. Need for reintervention was 19, 10, and 33 % in these groups, respectively (p = 0.123). No myomectomy cases had further intervention. At 5 years, the prevalence of new fibroid was 60 % in the myomectomy group and 7 % in the UAE group (p = 0.008). CONCLUSION: There is a further significant reduction in both uterine volume and dominant fibroid diameter between 6 months and 5 years after UAE. Complete fibroid infarction does not translate into total freedom from a subsequent reintervention. New fibroid formation is significantly higher after myomectomy.

Central venous access port devices - a pictorial review of common complications from the interventional radiology perspective.

Portacaths are tunnelled and totally implanted central venous access port devices (CVAPD). They are commonly used for intravenous antibiotic delivery in patients with cystic fibrosis. More recently, they are being used in oncology to deliver chemotherapy and apheresis. It is therefore important to be aware of portacath associated complications and their imaging features. This pictorial review illustrates and discusses common complications associated with Portacath devices.

British Society of Interventional Radiology Iliac Artery Angioplasty-Stent Registry III.

The objective of this study was to audit current practice in iliac artery intervention in the United Kingdom. In 2001 the British Society of Interventional Radiology Iliac Artery Angioplasty-Stent (BIAS) III registry provided the first national database for iliac intervention. It recommended that data collection needed to continue in order to facilitate the dissemination of comparative data to individual units. BIAS III was designed to continue this work and has a simplified data set with an online submission form. Interventionalists were invited to complete a 3-page tick sheet for all iliac angioplasties and stents. Questions covered risk factors, procedural data, and outcome. Data for 2233 patients were submitted from 37 institutions over a 43-month period. Consultants performed 80% of the procedures, 62% of which were for claudication. Fifty-four percent of lesions were treated with stents and 25% of patients underwent bilateral intervention, resulting in a residual stenosis of <50% in 98%. Ninety-seven percent of procedures had no limb complication and there was a 98% inpatient survival rate. In conclusion, these figures provide an essential benchmark for both audit and patient information. National databases need to be expanded across the range of interventional procedures, and their collection made simple and, preferably, online.

Critical lower-limb ischemia: the diagnostic performance of dual-phase injection MR angiography (including high-resolution distal imaging) compared with digital subtraction angiography.

PURPOSE: To prospectively compare contrast-enhanced (CE) magnetic resonance (MR) angiography against digital subtraction angiography (DSA) in patients with critical lower-limb ischemia. MATERIALS AND METHODS: Thirty patients with critical lower limb ischemia underwent both CE MR angiography and DSA. CE MR angiography commenced with a dedicated high-resolution study of the below-knee arteries followed by a three-station bolus-chase examination. Two blinded observers recorded the severity of the most significant stenosis within each arterial segment. Interobserver agreement was calculated and, with DSA as the reference standard, the sensitivity and specificity of CE MR angiography for the detection of significant stenosis (>or=50% luminal narrowing) or occlusion was calculated. RESULTS: All 390 arterial segments were scored by both observers. Sensitivity was higher in the distal segments (92%-96%) compared with the proximal segments (69%-79%). Specificity was similar in distal (90%-91%) and more proximal segments (86%-96%). Overall, interobserver agreement was excellent (kappa = 0.95 for CE MR angiography and DSA) and was superior within the distal segments. Twenty-eight segments that were considered occluded on DSA were shown to be patent on CE MR angiography and 16 segments that were considered occluded on CE MR angiography were shown to be patent on DSA. CONCLUSIONS: In patients with critical lower-limb ischemia, CE MR angiography with high-resolution distal imaging is highly accurate for assessment of the below-knee arteries. Both DSA and CE MR angiography may identify patent vessels that are considered occluded based on the other modality.

Case report: octreotide as an adjunct to embolisation in the management of recurrent bleeding upper gastrointestinal metastases from primary renal cell cancer.

The recommended treatment for patients with severe bleeding from upper gastrointestinal (GI) metastases is embolisation. We report a case in which despite adequate embolisation major haemorrhage from renal cell carcinoma (RCC) gastric metastases continually recurred. During a severe bleed refractory to embolisation octreotide was used to control and prevent further bleeding. No further episodes of severe haemorrhage occurred over the following 23 months since starting treatment. Octreotide has been observed to be effective both in the acute management of persistent haemorrhage and in prevention of subsequent haematemesis from GI metastatic RCC.

Uterine fibroids--do size and location determine menstrual blood loss?

OBJECTIVE: To investigate any potential effect of fibroid size and distribution on menstrual blood loss (MBL). STUDY DESIGN: Retrospective comparative study of 50 women with symptomatic fibroids who underwent uterine imaging and objective MBL measurement prior to uterine artery embolisation between 1999 and 2002. SETTING: West of Scotland Gynaecology and radiology departments. METHOD: Uterine imaging was by magnetic resonance imaging (MRI) in all but one case and MBL was performed using the alkaline haematin technique. Fibroid characteristics were assessed by an experienced radiologist unaware of the MBL measurements. RESULTS: Thirty-three (66%) women had objective menorrhagia with a MBL in excess of 80 ml per period. The commonest location of fibroids was intramural; these particular fibroids also had the largest diameter and the greatest uterine volume. There was a negative relationship between MBL and the diameter of the largest fibroid (r = -0.419, P < 0.01). All but two women (both of whom had subserosal fibroids alone) demonstrated distortion of the uterine cavity. All women with submucosal fibroids presented with menorrhagia. CONCLUSION: This study found that MBL correlated with neither fibroid size nor location. However, all the women with sub-mucosal fibroids had menorrhagia with a MBL greater than 80 ml.